Optimal Care of Complicated Appendicitis

When the appendix becomes infected and inflamed, it is called appendicitis. Sometimes, if the infection and inflammation get worse, the appendix can die or burst, leading to a larger infection or even pus pockets around the appendix. This is called complicated, or perforated, appendicitis. Three common treatments for complicated appendicitis are

• appendectomy (removal of the appendix) right away
• appendectomy several weeks after the diagnosis
• treating the appendicitis without performing an appendectomy

This study seeks to determine which of these three approaches is most cost-effective in children with complicated appendicitis.

Study Overview

• Status: Completed
• Conditions: Appendicitis; Complicated Appendicitis; Perforated Appendicitis; Ruptured Appendicitis
• Intervention / Treatment: Procedure: Early Appendectomy; Drug: Antibiotics; Procedure: Interval Appendectomy

Detailed Description

This is a single center, prospective study to compare early appendectomy vs. non-operative management of immunocompetent patients with complicated appendicitis, and then to compare interval appendectomy vs. no interval appendectomy in those managed with the initial non-operative approach. Patients who choose early appendectomy will have surgery within 24 hours of diagnosis and be discharged once they are afebrile for 24 hours, have a normal WBC count, and can tolerate a diet. They will be discharged with 5 days of oral ciprofloxacin and metronidazole and follow-up in clinic 2-4 weeks later. Patients who choose non-operative management will receive piperacillin-tazobactam with or without abscess drainage until they are afebrile 24 hours with a normal WBC count and are tolerating a diet, followed by 5 days of oral ciprofloxacin and metronidazole upon discharge. These patients will then be seen in clinic in 2-4 weeks, at which time they will be given the choice of whether or not to undergo interval appendectomy at least 8 weeks from initial presentation. Those in the interval appendectomy group will follow-up one month post-operatively. Patients in both groups will be contacted 3 months and 2 years following initial presentation.

{{{While 40 participants were enrolled as intended, and some data was collected from them, a combination of staff turnover and subsequent resource constraints did not permit the analysis originally intended. Thus, results data is shown comparing the early appendectomy participants against the other two arms combined.}}}}

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 15 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria

1. At least 1 of the following CT or MRI findings:

   1. Peri-appendicular abscess
   2. Extruded appendicolith
   3. Visible hole in appendiceal wall
   4. Free peritoneal air

   OR

2. CT or MRI read with phlegmon or diffuse/extensive inflammation/free fluid plus 1 of 3 of the following (with CT) or 2 of 3 of the following (with MRI) *:

   1. White blood cell count (WBC) >15
   2. Peritonitis (involuntary right lower quadrant (RLQ) guarding, + Rovsing sign, percussion tenderness, and/or rebound tenderness)
   3. Temperature > 38.0 C *>90% specificity for complicated appendicitis based on unpublished institutional data

Exclusion Criteria

1. Immunocompromized state
2. History of major abdominal operation
3. Previous appendicitis
4. Major comorbidities that preclude safe operation
5. Inability to follow-up or appropriately consent
6. Pregnant women

7. Allergy to penicillin plus any one of the following:

   1. Hypersensitivity to ciprofloxacin and/or metronidazole
   2. Pregnant/lactating women
   3. Patients taking theophylline
   4. Patient taking tizanidine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early Appendectomy	Procedure: Early Appendectomy; Removal of the appendix within 24 hours of admission; Drug: Antibiotics; Zosyn will be administered unless the patient has a penicillin allergy, in which case patients will receive both ciprofloxacin and metronidazole.; Other Names: Zosyn (piperacillin/tazobactam); ciprofloxacin; metronidazole
Experimental: Interval Appendectomy	Drug: Antibiotics; Zosyn will be administered unless the patient has a penicillin allergy, in which case patients will receive both ciprofloxacin and metronidazole.; Other Names: Zosyn (piperacillin/tazobactam); ciprofloxacin; metronidazole; Procedure: Interval Appendectomy; Removal of the appendix after initial antibiotic treatment and at least 6 weeks of recovery.
Experimental: No Appendectomy	Drug: Antibiotics; Zosyn will be administered unless the patient has a penicillin allergy, in which case patients will receive both ciprofloxacin and metronidazole.; Other Names: Zosyn (piperacillin/tazobactam); ciprofloxacin; metronidazole

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Cost of Care	Total health care cost starting from time of admission was the intention of this outcome measure. However, the institutions potentially involved were unwilling to provide access to any cost data so this could not be analyzed for any length of time.	The original intention was to gather cost data for 2 years per person following admission. As no cost data was able to be procured, there is no time frame to which it applies.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complications	Number of persons who experience any of a number of specified complications, including new/recurrent abscess, wound infection, small bowel obstruction, or need for a larger operation	During index/initial hospitalization (generally not more than 5-6 weeks)
Parents Away From Work	Parents away from work measured in days is presented here. The intention was to collect "missed activity days" for children as well as missed parent work days. However, the question to capture this information referred to school and was determined to be too inconsistent with the way the question may have been interpreted when the survey was given to code reliably.	During index/initial hospitalization (generally not more than 5-6 weeks)
Duration of Antibiotic Therapy	Duration of antibiotic therapy measured in days	During index/initial hospitalization (generally not more than 5-6 weeks)
Length of Stay	Length of all hospital stays measured in days	During index/initial hospitalization (generally not more than 5-6 weeks)
Number of Percutaneous Drainage Procedures	Number of persons with differing numbers of percutaneous drainage procedures	During index/initial hospitalization (generally not more than 5-6 weeks)
Number of Radiographic Imaging Studies	Number of radiographic imaging studies including ultrasound, CT, and MRI	During index/initial hospitalization (generally not more than 5-6 weeks)
Quality of Life (PedsQL)	Original QOL outcome measure listed was: Quality of life measured by PedsQL 2 years following discharge. Two year data collected was insufficient to allow for any analysis. One month GI QOL data collected, also listed in the protocol, is shown below. GI QoL is a validated measure with scores ranging from 0 to 100, where lower scores mean worse quality of life and higher scores mean better quality of life. Peds QL is a validated measure with scores ranging from 0 to 100, where lower scores mean worse quality of life and higher scores mean better quality of life.	1 month; for GI QOL; 2 years for Peds QL
Recurrent Appendicitis	Number of persons who experience recurrent appendicitis requiring hospitalization. Because the early appendectomy arm participant by definition have no appendix to infect after surgery, they are not shown below.	2 years; (Although this appears longer than trial duration, study completion date is based on last 2 year survey turned in, and medical record analysis looked a full two years per participant which extended a bit longer.)

Collaborators and Investigators

• Sponsor: University of Michigan
• Investigators: Principal Investigator: Steven W. Bruch, M.D., University of Michigan

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2017
• Primary Completion (Actual): March 26, 2020
• Study Completion (Actual): March 26, 2020

Study Registration Dates

• First Submitted: May 17, 2017
• First Submitted That Met QC Criteria: May 17, 2017
• First Posted (Actual): May 19, 2017

Study Record Updates

• Last Update Posted (Actual): November 28, 2023
• Last Update Submitted That Met QC Criteria: November 12, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Cecal Diseases; Intraabdominal Infections; Appendicitis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Cytochrome P-450 CYP1A2 Inhibitors; beta-Lactamase Inhibitors; Metronidazole; Anti-Bacterial Agents; Ciprofloxacin; Piperacillin; Tazobactam; Piperacillin, Tazobactam Drug Combination
• Other Study ID Numbers: HUM00103791

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No